Dichloromethyllithium

The heterocyclic scaffolds are prepared from pyroglutamic acid [154, 155]. 1-aminoalkyl boronic acid pinanediol esters are readily available through a diastereoselective homologation with dichloromethyllithium, providing (5)-a-chloroboronic esters. Aminolysis of the chloride yielded... 

DibromomethylUthium,LiCHBr2, dichloromethyllithium. Dibromomethyllithium can be generated from CH2Br2 with LDA as base rather than BuLi, used for generation of dichloromethyllithium from CH2C12. 

Spiro epoxides are also valuable intermediates for the synthesis of type I branched-chain sugars. These spiro epoxides are formed from ketosugars using diazomethane addition or sulfonium chemistry. Further ring opening of the epoxide allows the introduction of various nucleophiles [1], Chloro spiroepoxide 15 (Scheme 9) has been prepared recently from ketosugar 1 dichloromethyllithium [28]. 

K. Sato, K. Suzuki, M. Uead, M. Katayama, and Y. Kajihara, A novel reagent for the synthesis of branched-chain functionalized sugars, dichloromethyllithium, Chan. Lett. p. 1469 (1991). 

An alternate synthesis is outlined in Scheme 2.1 2 Diisopropyl dichloromethylboronate (6) is readily prepared by reacting triisopropyl borate with dichloromethyllithium prepared in situ. 20 Transesterification with a suitable C2 symmetric diol gives an ester 7 that can be treated with an alkylmagnesium bromide to yield chloride 8 and then, after transesterification with pinanediol (see Section 15.1.7.2) a product 9 which is analogous to 3. 

Application of the previously described reaction sequence allows an initial insertion reaction with dichloromethyllithium to give 20 Then 20 is enhanced by one C, residue using Grignard reagent 21 to produce 22. Another reaction with dichloromethyllithium results in a C chain extension to product 5. Since the insertion reaction with dichloromethyllithium was conducted twice, the distance between the boron atom and the PMB ether inemases by two carbon atoms. 

Reaction of boronic esters, RB(OR )2, with dichloromethyllithium, LiCHCl2, inserts the CHC1 unit into the carbon-boron bond of the boronic ester. This is known as boronic ester homologation. If boronic esters derived from homochiral alcohols are used in this reaction, then new homochiral centres may be generated as will be illustrated below. 

An extension of the synthetic applicability of lithium halomethanes is achieved by the simultanous presence of another main group heteroatom at the same carbon. Thus, if one of the chlorine atoms of dichloromethyllithium is replaced by a sulfonylamin group, the following products are obtained by reaction with electrophiles (Eq. (23)) 25). The substituted carbenoid can be converted to normal carbonyl adducts as well as to olefins and cyclopropanes. 

Alkynes. Primary alkyl halides react with dichloromethyllithium in the presence of HMPT (1 equiv.) to form homologated 1,1-dichloroalkanes in 60-90% yield. Several methods have been used for dehydrochlorination of the products. A new method is the reaction with 3 equiv. of n-butyllithium to form a lithium... 

Dichloro-3-methylbutane, 51 Dichloromethyllithium, 154 Dichloromethyl methyl ether, 69,154-... 

Reaction of chlorocarbene, generated from dichloromethyllithium, with the malono-nitrile derivative 187 affords minor amounts (2%) of the corresponding electrophilic cyclopropane (188) (equation 47). Reaction of phenyliodonium bis(methoxycarbonyl)... 

Chain extensions using an insertion reaction of dichloromethyllithium or dibromomethyllithium with (5 )-pinanediol [(benzyloxy)methyl]boronate 26 has been used to generate L-C3-, L-C4-and L-Cs-aldoses [51]. In order to obtain 2,3-di-O-benzyl-L-glyceraldehyde 27, the insertion reaction has to be applied twice (Scheme 13.20). By repeating the process two more times, L-ribose has been prepared with high enantiomeric purity [51]. 

Another route to terminal alkynes having one carbon more than the aldehyde precursor is via alkylation of primary alkyl bromides with dichloromethyllithium in the presence of HMPA to yield the 1,1-dichloroalkane. Subsequent dehydrochlorination with three equivalents of n-BuLi followed by hydrolytic workup affords the corresponding terminal alkyne. ... 

The incorporation of fluorine into biologically active compounds can greatly enhance their potency fluoroalkyl phosphonates are isosteres of the natural phosphonate monoesters. The alkylation chemistry of a-fluoro- and a,a-difluoro-alkyl phosphonates has been reported. Burton and Sprague have described the alkylation of (diethoxyphosphoryl)difluoromethylzinc bromide with allylic halides the reaction is catalyzed by copper(I) bromide. The alkylation of (diethoxyphosphoryl)dichloromethyllithium was reported by Normant and coworkers. The products can be transmetallated and further alkylated. 

Villieras and coworkers have contributed a considerable number of synthetic methods employing lithium halocarbenoids. An early example was the alkylation of dibromomethyllithium and higher homologs (Scheme 15). The anion (15) is easily generated from 1,1-dibromoalkanes by deprotonation with LDA in THF at low temperature. Alkenes can then be generated simply by treating the products with Bu"Li in EtjO, Alkylation of dichloromethyllithium with primary alkyl halides followed by reaction of the dichloroalkanes with Bu"Li represents a method for the preparation of 1 -alkynes. ... 

Boronic esters (8) react with dichloromethyllithium to form intermediate borate complexes which then undergo rearrangement to form 2-haloboronic esters (9). When treated with a Grignard reagent, the 2-haloboronic esters (9) rearrange to secondary alkylboronic esters (10 Scheme 3). 

Brown and coworkers have described an alternative synthesis of chiral alkylboronic esters. In this synthesis prochiral alkenes are hydroborated with monoisopinocamphenylborane to yield isopinocam-phenylalkylboranes which are then readily transformed to chiral alkyllraronic esters (Scheme 39). Homologation with dichloromethyllithium, followed by reduction with potassium triisopropoxyborohy-dride (KIPBH) and oxidation, finely yields B-chiral alcohols (Scheme 40). These alcohols are not easily prepared by other methods. Aldehydes can be prepared by homologation from chiral alkylboronic esters with LiCH(OMe)SPh and oxidation (Scheme 41). ... 

---